Method for producing triazolinethione derivatives

ABSTRACT

According to a novel process, it is possible to prepare triazolinethione derivatives of the formula 
     
       
         
         
             
             
         
       
     
     in which R 1  and R 2  are each as defined in the description 
     by 
     a) reacting hydrazine derivatives of the formula 
     
       
         
         
             
             
         
       
     
      with carbonyl compounds of the formula 
     
       
         
         
             
             
         
       
     
      in which R 3  and R 4  are each as defined in the description 
      with potassium thiocyanate, sodium thiocyanate or ammonium thiocyanate, 
      if appropriate in the presence of a diluent and if appropriate in the presence of an acid, and 
     b) reacting the resulting triazolidinethione derivatives of the formula 
     
       
         
         
             
             
         
       
     
      with formic acid, if appropriate in the presence of a catalyst and if appropriate in the presence of a diluent. 
     The triazolidinethione derivatives of the formula (V) are novel.

The present invention relates to a novel process for preparingtriazolinethione derivatives which are known as active compounds havingmicrobicidal, in particular fungicidal, properties.

It is already known that triazolinethione derivatives can be prepared byeither reacting the corresponding triazole derivatives successively withstrong bases and sulphur and then hydrolysing them, or reacting themdirectly with sulphur at high temperatures, followed by treatment withwater (cf. WO-A 96-16 048). However, this process has the disadvantagethat the desired products are obtained in only relatively low yields, orthat reaction conditions are required which are difficult to maintain onan industrial scale.

Furthermore, it has already been described that certain1,2,4-triazoline-5-thiones substituted in the 3 position can be preparedby reacting N-chlorothioformyl-N-(1-chloroalk-1-ene)-amines withcarbonylhydrazine derivatives (cf. DE-A 197 01 032, DE-A 196 01 189 andEP-A 0 784 053). However, the synthesis of corresponding substanceswhich do not have a substituent in the 3 position is not mentioned.

Furthermore, Bull. Chem. Soc. Japan 46, 2215 (1973) discloses thattriazolinethiones substituted in the 3 position can be synthesized byreacting phenylhydrazine with sodium thiocyanate and ketones oraldehydes in the presence of hydrochloric acid and treating theresulting triazolidinethiones substituted in the 3 position withoxidizing agents. This process has the disadvantages that very longreaction times are required and that no triazolinethiones which areunsubstituted in the 3 position can be obtained in this manner.

Finally, it is also known that2-(1-chloro-cyclopropyl)-1-(2-chloro-phenyl)-3-(1,2,4-triazol-1-yl)-propan-2-olis obtained when[1-(2-chloro-phenyl)-2-(1-chloro-cyclopropyl)-2-hydroxy]-propyl-1-hydrazineis reacted with formamidine acetate (cf. DE-A 40 30 039). However,thiono derivatives of triazoles are not obtainable by this method.

It has now been found that triazolinethione derivatives of the formula

in which

R¹ and R² are identical or different and each represents optionallysubstituted alkyl, optionally substituted alkenyl, optionallysubstituted cycloalkyl, optionally substituted aralkyl, optionallysubstituted aralkenyl, optionally substituted aroxyalkyl, optionallysubstituted aryl or optionally substituted heteroaryl,

can be prepared by

a) reacting, in a first step, hydrazine derivatives of the formula

 in which

R¹ and R² are each as defined above with carbonyl compounds of theformula

in which

R³ represents alkyl having 1 to 4 carbon atoms or represents phenyl and

R⁴ represents hydrogen or alkyl having 1 to 4 carbon atoms or

R³ and R⁴ together represent a —(CH₂)₅— chain and with thiocyanate ofthe formula

X—SCN  (IV),

in which

X represents sodium, potassium or ammonium,

if appropriate in the presence of a diluent and if appropriate in thepresence of an acid, and

b) reacting the resulting triazolidinethione derivatives of the formula

 in which

R¹, R², R³ and R⁴ are each as defined above

with formic acid, if appropriate in the presence of a catalyst and ifappropriate in the presence of a diluent.

It is extremely surprising that triazolinethione derivatives of theformula (I) can be prepared by the process according to the invention insubstantially higher yields or under considerably more simple conditionsthan by the prior-art methods. It is also unexpected that, when thesecond step of the process according to the invention is carried out,the exchange of the

for a methylene group occurs with high selectivity.

The process according to the invention has a number of advantages. Thus,as already mentioned, it makes it possible to synthesizetriazolinethiones of the formula (I) in high yield. It is alsofavourable that the required starting materials and reaction componentscan be prepared in a simple manner and are available even in relativelylarge amounts. Finally, a further advantage consists in the fact thatthe individual reaction steps can be carried out and the reactionproducts can be isolated without any problems.

Using2-(1-chloro-cyclopropyl)-3-(2-chloro-phenyl)-2-hydroxy-propyl-1-hydrazineas starting material and reacting this in the first step with acetoneand potassium thiocyanate and, in the second step, allowing theresulting triazolidinethione derivative to react with formic acid, thecourse of the process according to the invention can be illustrated bythe formula scheme below.

The formula (II) provides a general definition of the hydrazinederivatives required as starting materials for carrying out the processaccording to the invention. Preference is given to using compounds ofthe formula (II) in which

R¹ represents straight-chain or branched alkyl having 1 to 6 carbonatoms, where these radicals may be mono- to tetrasubstituted byidentical or different substituents from the group consisting ofhalogen, alkoxy having 1 to 4 carbon atoms, alkoximino having 1 to 4carbon atoms in the alkoxy moiety and cycloalkyl having 3 to 7 carbonatoms,

or

 represents straight-chain or branched alkenyl having 2 to 6 carbonatoms, where each of these radicals may be mono- to trisubstituted byidentical or different substituents from the group consisting ofhalogen, alkoxy having 1 to 4 carbon atoms and cycloalkyl having 3 to 7carbon atoms,

or

 represents cycloalkyl having 3 to 7 carbon atoms, where each of theseradicals may be mono- to trisubstituted by identical or differentsubstituents from the group consisting of halogen, cyano and alkylhaving 1 to 4 carbon atoms,

or

 represents aralkyl having 6 to 10 carbon atoms in the aryl moiety and 1to 4 carbon atoms in the straight-chain or branched alkyl moiety, wherethe aryl moiety may in each case be mono- to trisubstituted by identicalor different substituents from the group consisting of halogen, alkylhaving 1 to 4 carbon atoms, alkoxy having 1 to 4 carbon atoms, alkylthiohaving 1 to 4 carbon atoms, halogenoalkyl having 1 or 2 carbon atoms and1 to 5 identical or different halogen atoms, halogenoalkoxy having 1 or2 carbon atoms and 1 to 5 identical or different halogen atoms,halogenoalkylthio having 1 or 2 carbon atoms and 1 to 5 identical ordifferent halogen atoms, cycloalkyl having 3 to 7 carbon atoms, phenyl,phenoxy, alkoxycarbonyl having 1 to 4 carbon atoms in the alkoxy moiety,alkoximinoalkyl having 1 to 4 carbon atoms in the alkoxy moiety and 1 to4 carbon atoms in the alkyl moiety, nitro and cyano,

or

 represents aralkenyl having 6 to 10 carbon atoms in the aryl moiety and2 to 4 carbon atoms in the alkenyl moiety, where the aryl moiety may ineach case be mono- to trisubstituted by identical or differentsubstituents from the group consisting of halogen, alkyl having 1 to 4carbon atoms, alkoxy having 1 to 4 carbon atoms, alkylthio having 1 to 4carbon atoms, halogenoalkyl having 1 or 2 carbon atoms and 1 to 5identical or different halogen atoms, halogenoalkoxy having 1 or 2carbon atoms and 1 to 5 identical or different halogen atoms,halogenoalkylthio having 1 or 2 carbon atoms and 1 to 5 identical ordifferent halogen atoms, cycloalkyl having 3 to 7 carbon atoms, phenyl,phenoxy, alkoxycarbonyl having 1 to 4 carbon atoms in the alkoxy moiety,alkoximinoalkyl having 1 to 4 carbon atoms in the alkoxy moiety and 1 to4 carbon atoms in the alkyl moiety, nitro and cyano,

or

 represents aroxyalkyl having 6 to 10 carbon atoms in the aryl moietyand 1 to 4 carbon atoms in the straight-chain or branched oxyalkylmoiety, where the aryl moiety may in each case be mono- totrisubstituted by identical or different substituents from the groupconsisting of halogen, alkyl having 1 to 4 carbon atoms, alkoxy having 1to 4 carbon atoms, alkylthio having 1 to 4 carbon atoms, halogenoalkylhaving 1 or 2 carbon atoms and 1 to 5 identical or different halogenatoms, halogenoalkoxy having 1 or 2 carbon atoms and 1 to 5 identical ordifferent halogen atoms, halogenoalkylthio having 1 or 2 carbon atomsand 1 to 5 identical or different halogen atoms, cycloalkyl having 3 to7 carbon atoms, phenyl, phenoxy, alkoxycarbonyl having 1 to 4 carbonatoms in the alkoxy moiety, alkoximinoalkyl having 1 to 4 carbon atomsin the alkoxy moiety and 1 to 4 carbon atoms in the alkyl moiety, nitroand cyano,

or

 represents aryl having 6 to 10 carbon atoms, where each of theseradicals may be mono- to trisubstituted by identical or differentsubstituents from the group consisting of halogen, alkyl having 1 to 4carbon atoms, alkoxy having 1 to 4 carbon atoms, alkylthio having 1 to 4carbon atoms, halogenoalkyl having 1 or 2 carbon atoms and 1 to 5identical or different halogen atoms, halogenoalkoxy having 1 or 2carbon atoms and 1 to 5 identical or different halogen atoms,halogenoalkylthio having 1 or 2 carbon atoms and 1 to 5 identical ordifferent halogen atoms, cycloalkyl having 3 to 7 carbon atoms, phenyl,phenoxy, alkoxycarbonyl having 1 to 4 carbon atoms in the alkoxy moiety,alkoximinoalkyl having 1 to 4 carbon atoms in the alkoxy moiety and 1 to4 carbon atoms in the alkyl moiety, nitro and cyano,

or

 represents an optionally benzo-fused five- or six-memberedheteroaromatic radical having 1 to 3 heteroatoms, such as nitrogen,sulphur and/or oxygen, where each of these radicals may be mono- totrisubstituted by identical or different substituents from the groupconsisting of halogen, alkyl having 1 to 4 carbon atoms, hydroxyalkylhaving 1 to 4 carbon atoms, hydroxyalkinyl having 3 to 8 carbon atoms,alkoxy having 1 or 2 carbon atoms, alkylthio having 1 or 2 carbon atoms,halogenoalkyl, halogenoalkoxy and halogenoalkylthio having in each case1 or 2 carbon atoms and 1 to 5 identical or different halogen atoms,such as fluorine or chlorine atoms, formyl, dialkoxymethyl having 1 or 2carbon atoms in each alkoxy group, acyl having 2 to 4 carbon atoms,alkoxycarbonyl having 1 to 4 carbon atoms in the alkoxy moiety,alkoximinoalkyl having 1 to 4 carbon atoms in the alkoxy moiety and 1 to3 carbon atoms in the alkyl moiety, nitro and cyano, and

R² represents straight-chain or branched alkyl having 1 to 6 carbonatoms, where these radicals may be mono- to tetrasubstituted byidentical or different substituents from the group consisting ofhalogen, alkoxy having 1 to 4 carbon atoms, alkoximino having 1 to 4carbon atoms in the alkoxy moiety and cycloalkyl having 3 to 7 carbonatoms,

or

 represents straight-chain or branched alkyl having 2 to 6 carbon atoms,where each of these radicals may be mono- to trisubstituted by identicalor different substituents from the group consisting of halogen, alkoxyhaving 1 to 4 carbon atoms and cycloalkyl having 3 to 7 carbon atoms,

or

 represents cycloalkyl having 3 to 7 carbon atoms, where each of theseradicals may be mono- to trisubstituted by identical or differentsubstituents from the group consisting of halogen, cyano and alkylhaving 1 to 4 carbon atoms,

or

 represents aralkyl having 6 to 10 carbon atoms in the alkyl moiety and1 to 4 carbon atoms in the straight-chain or branched alkyl moiety,where the aryl moiety may in each case be mono- to trisubstituted byidentical or different substituents from the group consisting ofhalogen, alkyl having 1 to 4 carbon atoms, alkoxy having 1 to 4 carbonatoms, alkylthio having 1 to 4 carbon atoms, halogenoalkyl having 1 or 2carbon atoms and 1 to 5 identical or different halogen atoms,halogenoalkoxy having 1 or 2 carbon atoms and 1 to 5 identical ordifferent halogen atoms, halogenoalkylthio having 1 or 2 carbon atomsand 1 to 5 identical or different halogen atoms, cycloalkyl having 3 to7 carbon atoms, phenyl, phenoxy, alkoxycarbonyl having 1 to 4 carbonatoms in the alkoxy moiety, alkoximinoalkyl having 1 to 4 carbon atomsin the alkoxy moiety and 1 to 4 carbon atoms in the alkyl moiety, nitroand cyano,

or

 represents aralkenyl having 6 to 10 carbon atoms in the aryl moiety and2 to 4 carbon atoms in the alkenyl moiety, where the aryl moiety may ineach case be mono- to trisubstituted by identical or differentsubstituents from the group consisting of halogen, alkyl having 1 to 4carbon atoms, alkoxy having 1 to 4 carbon atoms, alkylthio having 1 to 4carbon atoms, halogenoalkyl having 1 or 2 carbon atoms and 1 to 5identical or different halogen atoms, halogenoalkoxy having 1 or 2carbon atoms and 1 to 5 identical or different halogen atoms,halogenoalkylthio having 1 or 2 carbon atoms and 1 to 5 identical ordifferent halogen atoms, cycloalkyl having 3 to 7 carbon atoms, phenyl,phenoxy, alkoxycarbonyl having 1 to 4 carbon atoms in the alkoxy moiety,alkoximinoalkyl having 1 to 4 carbon atoms in the alkoxy moiety and 1 to4 carbon atoms in the alkyl moiety, nitro and cyano,

or

 represents aroxyalkyl having 6 to 10 carbon atoms in the aryl moietyand 1 to 4 carbon atoms in the straight-chain or branched oxyalkylmoiety, where the aryl moiety may in each case be mono- totrisubstituted by identical or different substituents from the groupconsisting of halogen, alkyl having 1 to 4 carbon atoms, alkoxy having 1to 4 carbon atoms, alkylthio having 1 to 4 carbon atoms, halogenoalkylhaving 1 or 2 carbon atoms and 1 to 5 identical or different halogenatoms, halogenoalkoxy having 1 or 2 carbon atoms and 1 to 5 identical ordifferent halogen atoms, halogenoalkylthio having 1 or 2 carbon atomsand 1 to 5 identical or different halogen atoms, cycloalkyl having 3 to7 carbon atoms, phenyl, phenoxy, alkoxycarbonyl having 1 to 4 carbonatoms in the alkoxy moiety, alkoximinoalkyl having 1 to 4 carbon atomsin the alkoxy moiety and 1 to 4 carbon atoms in the alkyl moiety, nitroand cyano,

or

 represents aryl having 6 to 10 carbon atoms, where each of theseradicals may be mono- to trisubstituted by identical or differentsubstituents from the group consisting of halogen, alkyl having 1 to 4carbon atoms, alkoxy having 1 to 4 carbon atoms, alkylthio having 1 to 4carbon atoms, halogenoalkyl having 1 or 2 carbon atoms and 1 to 5identical or different halogen atoms, halogenoalkoxy having 1 or 2carbon atoms and 1 to 5 identical or different halogen atoms,halogenoalkylthio having 1 or 2 carbon atoms and 1 to 5 identical ordifferent halogen atoms, cycloalkyl having 3 to 7 carbon atoms, phenyl,phenoxy, alkoxycarbonyl having 1 to 4 carbon atoms in the alkoxy moiety,alkoximinoalkyl having 1 to 4 carbon atoms in the alkoxy moiety and 1 to4 carbon atoms in the alkyl moiety, nitro and cyano,

or

 represents an optionally benzo-fused five- or six-memberedheteroaromatic radical having 1 to 3 heteroatoms, such as nitrogen,sulphur and/or oxygen, where each of these radicals may be mono- totrisubstituted by identical or different substituents from the groupconsisting of halogen, alkyl having 1 to 4 carbon atoms, hydroxyalkylhaving 1 to 4 carbon atoms, hydroxyalkinyl having 3 to 8 carbon atoms,alkoxy having 1 or 2 carbon atoms, alkylthio having 1 or 2 carbon atoms,halogenoalkyl, halogenoalkoxy and halogenoalkylthio having in each case1 or 2 carbon atoms and 1 to 5 identical or different halogen atoms,such as fluorine or chlorine atoms, formyl, dialkoxymethyl having 1 or 2carbon atoms in each alkoxy group, acyl having 2 to 4 carbon atoms,alkoxycarbonyl having 1 to 4 carbon atoms in the alkoxy moiety,alkoximino alkyl having 1 to 4 carbon atoms in the alkoxy moiety and 1to 3 carbon atoms in the alkyl moiety, nitro and cyano.

Particular preference is given to using hydrazine derivatives of theformula (II) in which

R¹ represents straight-chain or branched alkyl having 1 to 4 carbonatoms, where these radicals may be mono- to tetrasubstituted byidentical or different substituents from the group consisting offluorine, chlorine, bromine, methoxy, ethoxy, propoxy, isopropoxy,alkoximino having 1 or 2 carbon atoms in the alkoxy moiety, cyclopropyl,cyclobutyl, cyclopentyl and cyclohexyl,

or

 represents straight-chain or branched alkenyl having 2 to 5 carbonatoms, where each of these radicals may be mono- to trisubstituted byidentical or different substituents from the group consisting offluorine, chlorine, bromine, methoxy, ethoxy, propoxy, isopropoxy,cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl,

or

 represents cycloalkyl having 3 to 6 carbon atoms, where each of theseradicals may be mono- to trisubstituted by identical or differentsubstituents from the group consisting of fluorine, chlorine, bromine,cyano, methyl, ethyl, propyl, isopropyl and tert-butyl,

or

 represents phenylalkyl having 1 to 4 carbon atoms in the straight-chainor branched alkyl moiety, where the phenyl moiety may be mono- totrisubstituted by identical or different substituents from the groupconsisting of fluorine, chlorine, bromine, methyl, ethyl, tert-butyl,methoxy, ethoxy, methylthio, trifluoromethyl, trifluoromethoxy,trifluoromethylthio, chlorodifluoromethoxy, difluoromethoxy,chlorodifluoromethylthio, methoxycarbonyl, ethoxycarbonyl,methoximinomethyl, 1-methoximinoethyl, nitro and cyano,

or

 represents phenylalkenyl having 2 to 4 carbon atoms in the alkenylmoiety, where the phenyl moiety may be mono- to trisubstituted byidentical or different substituents from the group consisting offluorine, chlorine, bromine, methyl, ethyl, tert-butyl, methoxy, ethoxy,methylthio, trifluoromethyl, trifluoromethoxy, trifluoromethylthio,chlorodifluoromethoxy, difluoromethoxy, chlorodifluoromethylthio,methoxycarbonyl, ethoxycarbonyl, methoximinomethyl, 1-methoximinoethyl,nitro and cyano,

or

 represents phenoxyalkyl having 1 to 4 carbon atoms in thestraight-chain or branched oxyalkyl moiety, where the phenyl moiety maybe mono- to trisubstituted by identical or different substituents fromthe group consisting of fluorine, chlorine, bromine, methyl, ethyl,tert-butyl, methoxy, ethoxy, methylthio, trifluoromethyl,trifluoromethoxy, trifluoromethylthio, chlorodifluoromethoxy,difluoromethoxy, chlorodifluoromethylthio, methoxycarbonyl,ethoxycarbonyl, methoximinomethyl, 1-methoximinoethyl, nitro and cyano,

or

 represents phenyl which may be mono- to trisubstituted by identical ordifferent substituents from the group consisting of fluorine, chlorine,bromine, methyl, ethyl, tert-butyl, methoxy, ethoxy, methylthio,trifluoromethyl, trifluoromethoxy, trifluoromethylthio,chlorodifluoromethoxy, difluoromethoxy, chlorodifluoromethylthio,methoxycarbonyl, ethoxycarbonyl, methoximinomethyl, 1-methoximinoethyl,nitro and cyano,

or

 represents pyrazolyl, imidazolyl, 1,2,4-triazolyl, pyrrolyl, furanyl,thienyl, thiazolyl, oxazolyl, pyridinyl, pyrimidinyl, triazinyl,quinolinyl, isoquinolinyl, quinazolinyl, indolyl, benzothienyl,benzofuranyl, benzothiazolyl or benzimidazolyl, where each of theseradicals may be mono- to trisubstituted by identical or differentsubstituents from the group consisting of fluorine, chlorine, bromine,methyl, ethyl, tert-butyl, methoxy, ethoxy, methylthio, trifluoromethyl,trifluoromethoxy, trifluoromethylthio, chlorodifluoromethoxy,chlorodifluoromethylthio, hydroxymethyl, hydroxyethyl, hydroxyalkinylhaving 4 to 6 carbon atoms, methoxycarbonyl, ethoxycarbonyl,methoximinomethyl, 1-methoximinoethyl, nitro, cyano, formyl,dimethoxymethyl, acetyl and propionyl, and

R² represents straight-chain or branched alkyl having 1 to 4 carbonatoms, where these radicals may be mono- to tetrasubstituted byidentical or different substituents from the group consisting offluorine, chlorine, bromine, methoxy, ethoxy, propoxy, isopropoxy,alkoximino having 1 or 2 carbon atoms in the alkoxy moiety, cyclopropyl,cyclobutyl, cyclopentyl and cyclohexyl,

or

 represents straight-chain or branched alkenyl having 2 to 5 carbonatoms, where each of these radicals may be mono- to trisubstituted byidentical or different substituents from the group consisting offluorine, chlorine, bromine, methoxy, ethoxy, propoxy, isopropoxy,cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl,

or

 represents cycloalkyl having 3 to 6 carbon atoms, where each of theseradicals may be mono- to trisubstituted by identical or differentsubstituents from the group consisting of fluorine, chlorine, bromine,cyano, methyl, ethyl, propyl, isopropyl and tert-butyl,

or

 represents phenylalkyl having 1 to 4 carbon atoms in the straight-chainor branched alkyl moiety, where the phenyl moiety may be mono- totrisubstituted by identical or different substituents from the groupconsisting of fluorine, chlorine, bromine, methyl, ethyl, tert-butyl,methoxy, ethoxy, methylthio, trifluoromethyl, trifluoromethoxy,trifluoromethylthio, chlorodifluoromethoxy, difluoromethoxy,chlorodifluoromethylthio, methoxycarbonyl, ethoxycarbonyl,methoximinomethyl, 1-methoximinoethyl, nitro and cyano,

or

 represents phenylalkenyl having 2 to 4 carbon atoms in the alkenylmoiety, where the phenyl moiety may be mono- to trisubstituted byidentical or different substituents from the group consisting offluorine, chlorine, bromine, methyl, ethyl, tert-butyl, methoxy, ethoxy,methylthio, trifluoromethyl, trifluoromethoxy, trifluoromethylthio,chlorodifluoromethoxy, difluoromethoxy, chlorodifluoromethylthio,methoxycarbonyl, ethoxycarbonyl, methoximinomethyl, 1-methoximinoethyl,nitro and cyano,

or

 represents phenoxyalkyl having 1 to 4 carbon atoms in thestraight-chain or branched oxyalkyl moiety, where the phenyl moiety maybe mono- to trisubstituted by identical or different substituents fromthe group consisting of fluorine, chlorine, bromine, methyl, ethyl,tert-butyl, methoxy, ethoxy, methylthio, trifluoromethyl,trifluoromethoxy, trifluoromethylthio, chlorodifluoromethoxy,difluoromethoxy, chlorodifluoromethylthio, methoxycarbonyl,ethoxycarbonyl, methoximinomethyl, 1-methoximinoethyl, nitro and cyano,

or

 represents phenyl which may be mono- to trisubstitued by identical ordifferent substituents from the group consisting of fluorine, chlorine,bromine, methyl, ethyl, tert-butyl, methoxy, ethoxy, methylthio,trifluoromethyl, trifluoromethoxy, trifluoromethylthio,chlorodifluoromethoxy, difluoromethoxy, chlorodifluoromethylthio,methoxycarbonyl, ethoxycarbonyl, methoximinomethyl, 1-methoximinoethyl,nitro and cyano,

or

 represents pyrazolyl, imidazolyl, 1,2,4-triazolyl, pyrrolyl, furanyl,thienyl, thiazolyl, oxazolyl, pyridinyl, pyrimidinyl, triazinyl,quinolinyl, isoquinolinyl, quinazolinyl, indolyl, benzothienyl,benzofuranyl, benzothiazolyl or benzimidazolyl, where each of theseradicals may be mono- to trisubstituted by identical or differentsubstituents from the group consisting of fluorine, chlorine, bromine,methyl, ethyl, tert-butyl, methoxy, ethoxy, methylthio, trifluoromethyl,trifluoromethoxy, trifluoromethylthio, chlorodifluoromethoxy,chlorodifluoromethylthio, hydroxymethyl, hydroxyethyl, hydroxyalkinylhaving 4 to 6 carbon atoms, methoxycarbonyl, ethoxycarbonyl,methoximinomethyl, 1-methoximinoethyl, nitro, cyano, formyl,dimethoxymethyl, acetyl and propionyl.

Very particular preference is given to using hydrazine derivatives ofthe formula (II) in which

R¹ represents n-propyl, isopropyl, n-butyl, i-butyl, sec-butyl ortert-butyl, where these radicals may be mono- to tetrasubstituted byidentical or different substituents from the group consisting offluorine, chlorine, bromine, methoxy, ethoxy, propoxy, isopropoxy,methoximino, ethoximino, cyclopropyl, cyclobutyl, cyclopentyl andcyclohexyl,

or

 represents straight-chain or branched alkenyl having 2 to 5 carbonatoms, where each of these radicals may be mono- to trisubstituted byidentical or different substituents from the group consisting offluorine, chlorine, bromine, methoxy, ethoxy, propoxy, isopropoxy,cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl,

or

 represents 1-methyl-cyclohexyl, cyclohexyl, 1-chloro-cyclopropyl,1-fluoro-cyclopropyl, 1-methyl-cyclopropyl, 1-cyano-cyclopropyl,cyclopropyl, 1-methyl-cyclopentyl or 1-ethyl-cyclopentyl,

or

 represents phenylalkyl having 1 or 2 carbon atoms in the straight-chainor branched alkyl moiety, where the phenyl moiety may be mono- totrisubstituted by identical or different substituents from the groupconsisting of fluorine, chlorine, bromine, methyl, ethyl, tert-butyl,methoxy, ethoxy, methylthio, trifluoromethyl, trifluoromethoxy,trifluoromethylthio, chlorodifluoromethoxy, difluoromethoxy,chlorodifluoromethylthio, methoxycarbonyl, ethoxycarbonyl,methoximinomethyl, 1-methoximinoethyl, nitro and cyano,

or

 represents phenylalkenyl having 2 to 4 carbon atoms in the alkenylmoiety, where the phenyl moiety may be mono- to trisubstituted byidentical or different substituents from the group consisting offluorine, chlorine, bromine, methyl, ethyl, tert-butyl, methoxy, ethoxy,methylthio, trifluoromethyl, trifluoromethoxy, trifluoromethylthio,chlorodifluormethoxy, difluoromethoxy, chlorodifluoromethylthio,methoxycarbonyl, ethoxycarbonyl, methoximinomethyl, 1-methoximinoethyl,nitro and cyano,

or

 represents phenoxyalkyl having 1 to 4 carbon atoms in thestraight-chain or branched oxyalkyl moiety, where the phenyl moiety maybe mono- to trisubstituted by identical or different substituents fromthe group consisting of fluorine, chlorine, bromine, methyl, ethyl,tert-butyl, methoxy, ethoxy, methylthio, trifluoromethyl,trifluoromethoxy, trifluormethylthio, chlorodifluoromethoxy,difluoromethoxy, chlorodifluoromethylthio, methoxycarbonyl,ethoxycarbonyl, methoximinomethyl, 1-methoximinoethyl, nitro and cyano,

or

 represents phenyl which may be mono- to trisubstituted by identical ordifferent substituents from the group consisting of fluorine, chlorine,bromine, methyl, ethyl, tert-butyl, methoxy, ethoxy, methylthio,trifluoromethyl, trifluoromethoxy, trifluoromethylthio,chlorodifluoromethoxy, difluoromethoxy, chlorodifluoromethylthio,methoxycarbonyl, ethoxycarbonyl, methoximinomethyl, 1-methoximinoethyl,nitro and cyano,

or

 represents pyrazolyl, imidazolyl, 1,2,4-triazolyl, pyrrolyl, furanyl,thienyl, thiazolyl, oxazolyl, pyridinyl, pyrimidinyl, triazinyl,quinolinyl, isoquinolinyl, quinazolinyl, indolyl, benzothienyl,benzofuranyl, benzothiazolyl or benzimidazolyl, where each of theseradicals may be mono- to trisubstituted by identical or differentsubstituents from the group consisting of fluorine, chlorine, bromine,methyl, ethyl, tert-butyl, methoxy, ethoxy, methylthio, trifluoromethyl,trifluoromethoxy, trifluoromethylthio, chlorodifluoromethoxy,chlorodifluoromethylthio, hydroxymethyl, hydroxyethyl, hydroxyalkinylhaving 4 to 6 carbon atoms, methoxycarbonyl, ethoxycarbonyl,methoximinomethyl, 1-methoximinoethyl, nitro, cyano, formyl,dimethoxymethyl, acetyl and propionyl, and

R² represents n-propyl, isopropyl, n-butyl, i-butyl, sec-butyl ortert-butyl, where these radicals may be mono- to tetrasubstituted byidentical or different substituents from the group consisting offluorine, chlorine, bromine, methoxy, ethoxy, propoxy, isopropoxy,methoximino, ethoximino, cyclopropyl, cyclobutyl, cyclopentyl andcyclohexyl,

or

 represents straight-chain or branched alkenyl having 2 to 5 carbonatoms, where each of these radicals may be mono- to trisubstituted byidentical or different substituents from the group consisting offluorine, chlorine, bromine, methoxy, ethoxy, propoxy, isopropoxy,cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl,

or

 represents 1-methyl-cyclohexyl, cyclohexyl, 1-chloro-cyclopropyl,1-fluoro-cyclopropyl, 1-methyl-cyclopropyl, 1-cyano-cyclopropyl,cyclopropyl, 1-methyl-cyclopentyl or 1-ethyl-cyclopentyl,

or

 represents phenylalkyl having 1 or 2 carbon atoms in the straight-chainor branched alkyl moiety, where the phenyl moiety may be mono- totrisubstituted by identical or different substituents from the groupconsisting of fluorine, chlorine, bromine, methyl, ethyl, tert-butyl,methoxy, ethoxy, methylthio, trifluoromethyl, trifluoromethoxy,trifluoromethylthio, chlorodifluormethoxy, difluoromethoxy,chlorodifluoromethylthio, methoxycarbonyl, ethoxycarbonyl,methoximinomethyl, 1-methoximinoethyl, nitro and cyano,

or

 represents phenylalkenyl having 2 to 4 carbon atoms in the alkenylmoiety, where the phenyl moiety may be mono- to trisubstituted byidentical or different substituents from the group consisting offluorine, chlorine, bromine, methyl, ethyl, tert-butyl, methoxy, ethoxy,methylthio, trifluoromethyl, trifluoromethoxy, trifluoromethylthio,chlorodifluoromethoxy, difluoromethoxy, chlorodifluoromethylthio,methoxycarbonyl, ethoxycarbonyl, methoximinomethyl, 1-methoximinoethyl,nitro and cyano,

or

 represents phenoxyalkyl having 1 to 4 carbon atoms in thestraight-chain or branched oxyalkyl moiety, where the phenyl moiety maybe mono- to trisubstituted by identical or different substituents fromthe group consisting of fluorine, chlorine, bromine methyl, ethyl,tert-butyl, methoxy, ethoxy, methylthio, trifluoromethyl,trifluoromethoxy, trifluoromethylthio, chlorodifluoromethoxy,difluoromethoxy, chlorodifluoromethylthio, methoxycarbonyl,ethoxycarbonyl, methoximinomethyl, 1-methoximinoethyl, nitro and cyano,

or

 represents phenyl which may be mono- to trisubstituted by identical ordifferent substituents from the group consisting of fluorine, chlorine,bromine, methyl, ethyl, tert-butyl, methoxy, ethoxy, methylthio,trifluoromethyl, trifluoromethoxy, trifluoromethylthio,chlorodifluoromethoxy, difluoromethoxy, chlorodifluoromethylthio,methoxycarbonyl, ethoxycarbonyl, methoximinomethyl, 1-methoximinoethyl,nitro and cyano,

or

 represents pyrazolyl, imidazolyl, 1,2,4-triazolyl, pyrrolyl, furanyl,thienyl, thiazolyl, oxazolyl, pyridinyl, pyrimidinyl, triazinyl,quinolinyl, isoquinolinyl, quinazolinyl, indolyl, benzothienyl,benzofuranyl, benzothiazolyl or benzimidazolyl, where each of theseradicals may be mono- to trisubstituted by identical or differentsubstituents from the group consisting of fluorine, chlorine, bromine,methyl, ethyl, tert-butyl, methoxy, ethoxy, methylthio, trifluoromethyl,trifluoromethoxy, trifluoromethylthio, chlorodifluoromethoxy,chlorodifluoromethylthio, hydroxymethyl, hydroxyethyl, hydroxyalkinylhaving 4 to 6 carbon atoms, methoxycarbonyl, ethoxycarbonyl,methoximinomethyl, 1-methoximinoethyl, nitro, cyano, formyl,dimethoxymethyl, acetyl and/propionyl.

The hydrazine derivatives of the formula (II) are known or can beprepared by processes known in principle (cf. DE-A-40 30 039).

Thus, hydrazine derivatives of the formula (II) are obtained by reacting1-chloro-2-hydroxy-ethane derivatives of the formula

or oxirane derivatives of the formula

in which

R¹ and R² are each as defined above with hydrazine hydrate, ifappropriate in the presence of a diluent.

The 1-chloro-2-hydroxy-ethane derivatives of the formula (VI) and alsothe oxirane derivatives of the formula (VII) are known or can beprepared by processes known in principle (cf. DE-A40 30 039 and EP-A 0297 345).

Suitable diluents for the above process for preparing hydrazinederivatives of the formula (II) are all customary inert organicsolvents. Preference is given to using alcohols, such as methanol,ethanol or n-butanol, furthermore ethers, such as dioxane or methyltert-butyl ether, and also aromatic hydrocarbons, such as benzene,toluene or xylene. However, it is also possible to carry out thereaction without any additional solvent. In this case, an excess ofhydrazine hydrate is employed, so that it acts both as reactioncomponent and as diluent.

When carrying out the preparation of hydrazine derivatives of theformula (III) according to the above process, the reaction temperaturescan be varied within a certain range. In general, the process is carriedout at temperatures between 60° C. and 120° C., preferably between 70°C. and 110° C.

In the preparation of hydrazine derivatives of the formula (II)according to the above process, in general from 1 to 20 mol, preferablyfrom 5 to 15 mol, of hydrazine hydrate are employed per mole of1-chloro-2-hydroxy-ethane derivative of the formula (VI) or of oxiranederivative of the formula (VII). Work-up is carried out by customarymethods. In general, the reaction mixture is admixed with an organicsolvent which is sparingly water-miscible, such as methyl tert-butylether or toluene, the aqueous phase is removed and the organic phase iswashed and dried.

The formula (III) provides a general definition of the carbonylcompounds required as reaction components for carrying out the firststep of the process according to the invention. Preference is given tousing carbonyl compounds of the formula (III) in which

R³ represents methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl orphenyl and

R⁴ represents hydrogen, methyl, ethyl, n-propyl or n-butyl or

R³ and R⁴ together represent a —(CH₂)₅— chain.

Particular preference is given to carbonyl compounds of the formula(III) in which

R³ represents methyl, ethyl, n-propyl, isopropyl, tert-butyl or phenyland

R⁴ represents hydrogen, methyl, ethyl or n-propyl or

R³ and R⁴ together represent a —(CH₂)₅— chain.

Examples of carbonyl compounds of the formula (III) which may bementioned are:

acetaldehyde

propionaldehyde

benzaldehyde

acetone

diethyl ketone

methyl ethyl ketone

di-n-propyl ketone

pinacolone

acetophenone and

cyclohexanone.

The carbonyl compounds of the formula (III) and also the thiocyanates ofthe formula (IV) are known.

Suitable diluents for carrying out the first step of the processaccording to the invention are all inert organic solvents which arecustomary for such reactions. Preference is given to using aromatichydrocarbons, such as benzene, toluene or xylene, furthermore ethers,such as dioxane, methyl tert-butyl ether, 1,2-dimethoxy-ethane or methyltert-amyl ether, moreover esters, such as ethyl acetate or butylacetate, and also alcohols, such as propanol, butanol or pentanol.However, excess carbonyl compound of the formula (III) may also act asdiluent.

Suitable acids for carrying out the first step of the process accordingto the invention are customary inorganic or organic acids. Preference isgiven to using hydrochloric acid, sulphuric acid or p-toluenesulphonicacid.

When carrying out the first step of the process according to theinvention, the reaction temperatures can be varied within a relativelywide range. In general, the reaction is carried out at temperaturesbetween 0° C. and 120° C., preferably between 10° C. and 110° C.

Both the first and the second step of the process according to theinvention are generally carried out under atmospheric pressure. However,it is also possible to operate under elevated pressure or, if no gaseouscomponents are involved in the reaction, under reduced pressure.

When carrying out the first step of the process according to theinvention, generally 1 to 2 mol of carbonyl compound of the formula(III) and 1 to 2 mol of thiocyanate of the formula (IV) are employed permole of hydrazine derivative of the formula (II). Work-up is carried outby customary methods. In general, the reaction mixture is washed withwater, the organic phase is dried and concentrated and the residue thatremains is freed from undesirable components by customary methods, forexample by recrystallization.

The formula (V) provides a general definition of the triazolidinethionederivatives required as starting materials for carrying out the secondstep of the process according to the invention. In this formula, R¹, R²,R³ and R⁴ each preferably have those meanings which have already beenmentioned in connection with the description of the hydrazinederivatives of the formula (II) or the carbonyl compounds of the formula(III) as being preferred for these radicals.

The triazolidinethione derivatives of the formula (V) have hitherto notbeen disclosed. They can be prepared by the reaction of the first stepof the process according to the invention.

Suitable catalysts for carrying out the second step of the processaccording to the invention are all reaction promoters which arecustomary for such reactions. Preference is given to using acids, suchas hydrochloric acid, sulphuric acid or p-toluenesulphonic acid, andalso metal oxides, such as amorphous titanium dioxide.

Suitable diluents for carrying out the second step of the processaccording to the invention are all weakly polar organic solvents whichare customary for such reactions. Preference is given to using alcohols,such as propanol, butanol or pentanol, furthermore esters, such as ethylacetate, butyl acetate or isobutyl formate, moreover ethers, such as1,2-dimethoxyethane, methyl tert-butyl ether or methyl tert-amyl ether,and also an excess of formic acid.

When carrying out the second step of the process according to theinvention, the reaction temperature can be varied within a certainrange. In general, the reaction is carried out at temperatures between80° C. and 150° C., preferably between 90° C. and 130° C.

When carrying out the second step of the process according to theinvention, an excess, in general from 5 to 50 mol, of formic acid and,if appropriate, a small amount of catalyst is employed per mole oftriazolidinethione derivative of the formula (V). Work-up is carried outby customary methods. In general, the reaction mixture is, ifappropriate after prior dilution with an organic solvent which issparingly water-miscible, extracted with aqueous hydrochloric acid, andthe organic phase is dried and concentrated. Any impurities which maythen still be present can be removed by customary methods, such asrecrystallization.

In a particular variant, the process according to the invention can becarried out such that 1-chloro-2-hydroxy-ethane derivatives of theformula (VI) or oxirane derivatives of the formula (VII) are reactedwith hydrazine hydrate and the resulting hydrazine derivatives of theformula (II) are then reacted further without prior isolation andpurification. Accordingly, triazolinethione derivatives of the formula(I) can also be prepared by

reacting 1-chloro-2-hydroxy-ethane derivatives of the formula

 or oxirane derivatives of the formula

 in which

R¹ and R² are each as defined above with hydrazine hydrate, ifappropriate in the presence of a diluent, and reacting the resulting

hydrazine derivatives of the formula

 in which

R¹ and R² are each as defined above without prior isolation withcarbonyl compounds of the formula

 in which

R³ represents alkyl having 1 to 4 carbon atoms or represents phenyl and

R⁴ represents hydrogen or alkyl having 1 to 4 carbon atoms or

R³ and R⁴ together represent a —(CH₂)₅— chain, and with thiocyanate ofthe formula

X—SCN  (IV)

 in which

X represents sodium, potassium or ammonium,

if appropriate in the presence of a diluent and if appropriate in thepresence of an acid, and

reacting the resulting triazolidinethione derivatives of the formula

in which

R¹, R², R³ and R⁴ are each as defined above with formic acid, ifappropriate in the presence of a catalyst and if appropriate in thepresence of a diluent.

The individual steps of this process are carried out in the manneralready described above.

The triazolinethione derivatives preparable according to the inventioncan be present in the “thiono” form of the formula

or in the tautomeric “mercapto” form of the formula

For the sake of simplicity, only the “thiono” form is shown in eachcase.

The triazolinethione derivatives preparable according to the inventionare known as active compounds having microbicidal, in particularfungicidal, properties (cf. WO-A 96-16 048).

The practice of the process according to the invention is illustrated bythe examples below.

PREPARATION EXAMPLES Example 1

a) Preparation of the compound of the formula

 At room temperature and with stirring, a mixture of 27.5 g (0.1 mol) of2-(1-chloro-cyclopropyl)-3-(2-chloro-phenyl)-2-hydroxy-propyl-1-hydrazineand 300 ml of 2N aqueous hydrochloric acid is initially admixed with 8.2g (0.14 mol) of acetone and then with 13.6 g (0.14 mol) of potassiumthiocyanate. The reaction mixture is then admixed with 100 ml of tolueneand stirred at room temperature for another 10 hours. The resultingsolid is then filtered off, washed with water and then with toluene anddried. In this manner, 30.7 g (82.1% of theory) of thetriazolidinethione derivative are obtained in the form of a colourlesscrystalline solid of melting point 186 to 189° C.

b) Preparation of the compound of the formula

 At room temperature and with stirring, a mixture of 92 g of formic acidand 100 ml of isobutyl formate is admixed with 18.7 g (0.05 mol) of thetriazolidinethione derivative described under a). After the addition hasended, the reaction mixture is heated under reflux for 17 hours, thenconcentrated by distilling off excess formic acid and solvent andfinally freed of volatile components under high vacuum. The product thatremains is dissolved in toluene, the resulting solution is washed withwater, and the organic phase is dried over sodium sulphate andconcentrated by distilling off the solvent. In this manner, 14.2 g (76%of theory) of2-(1-chloro-cyclopropyl)-1-(2-chloro-phenyl)-3-(4,5-dihydro-1,2,4-triazole-5-thiono-1-yl)-propyl-2-olare obtained in the form of a solid of melting point 138 to 139° C.

Example 2

At room temperature and with stirring, 22 g (=0.05 mol) of a productcomprising 63.7% of 1-chloro-2-hydroxy-ethane are added dropwise over aperiod of 15 minutes to 25 g (0.5 mol) of hydrazine hydrate. After theaddition has ended, the reaction mixture is stirred at 100° C. for 2hours and then cooled to room temperature. The resulting mixture isstirred into 100 ml of water and the aqueous phase is decanted off fromthe solid precipitate. This process is repeated once more using 100 mlof water. The resulting product is admixed with 150 ml of 2N aqueoushydrochloric acid, 4.1 g (0.07 mol) of acetone, 6.8 g (0.07 mol) ofpotassium thiocyanate and 50 ml of toluene. The reaction mixture isstirred at room temperature for 12 hours and then filtered. The filterresidue is washed successively with water and toluene and then dried. Inthis manner, 11.6 g of triazolidinethione derivative of theabovementioned formula are obtained in the form of a colourlesscrystalline solid of melting point 186 to 187° C. The calculated yieldis 62.0% of theory, based on the 1-chloro-2-hydroxy-ethane employed.

The triazolidinethione derivatives listed in the table below arelikewise prepared by the method given in Example 2.

TABLE 1 (Va)

Ex. Melting point Yield in % No. R³ R⁴ [° C.] of theory 3 —CH₃ H 143-14652.6 4 —CH₃ —C₂H₅ 167 (decomp.) 72.5 5

—CH₃ 174 (decomp.) 66.4 6 —(CH₂)₅— 194-196 67.9 (decomp.) 7 —C(CH₃)₃—CH₃ 137 (decomp.) 59.3 8 —CH(CH₃)₂ —CH₃ 146-152 68.2 9

H 176 38  

COMPARATIVE EXAMPLES Example A

At −20° C., a mixture of 3.12 g (10 mmol) of2-(1-chloro-cyclopropyl)-1-(2-chlorophenyl)-3-(1,2,4-triazol-1-yl)-propan-2-oland 45 ml of absolute tetrahydrofuran is admixed with 8.4 ml (21 mmol)of n-butyl-lithium in hexane and stirred at 0° C. for 30 minutes. Thereaction mixture is then cooled to −70° C., admixed with 0.32 g of (10mmol) of sulphur powder and stirred at −70° C. for 30 minutes. Themixture is warmed to −10° C., admixed with ice-water and adjusted to pH5 by addition of dilute sulphuric acid. The mixture is extractedrepeatedly with ethyl acetate, and the combined organic phases are driedover sodium sulphate and concentrated under reduced pressure. In thismanner, 3.2 g of a product which, according to gaschromatographicanalysis, comprises 95% of2-(1-chloro-cyclopropyl)-1-(2-chloro-phenyl)-3-(4,5-dihydro-1,2,4-triazol-5-thiono-1-yl)-propan-2-olare obtained. Recrystallization from toluene gives this substance as asolid which melts at from 138 to 139° C.

Example B

With stirring, a mixture of 3.12 g (10 mmol) of2-(1-chloro-cyclopropyl)-1-(2-chloro-phenyl)-3-(1,2,4-triazol-1-yl)-propan-2-ol,0.95 g (30 mmol) of sulphur powder and 20 ml of absoluteN-methyl-pyrrolidone is heated at 200° C. for 44 hours. The reactionmixture is then concentrated under reduced pressure (0.2 mbar). Theresulting crude product (3.1 g) is recrystallized from toluene. In thismanner, 0.7 g (20% of theory) of2-(1-chloro-cyclopropyl)-1-(2-chlorophenyl)-3-(4,5-dihydro-1,2,4-triazol-5-thiono-1-yl)-propan-2-olis obtained in the form of a solid which melts at 138-139° C.

What is claimed is:
 1. A process for preparing a triazolinethionederivative of the formula

in which R¹ and R² are identical or different and each representsoptionally substituted alkyl, optionally substituted alkenyl, optionallysubstituted cycloalkyl, optionally substituted aralkyl, optionallysubstituted aralkenyl, optionally substituted aroxyalkyl, optionallysubstituted aryl or optionally substituted heteroaryl, comprisingreacting a) in a first step, a hydrazine derivative of the formula

 in which  R¹ and R² are each as defined above with a carbonyl compoundof the formula

 in which R³ represents alkyl having 1 to 4 carbon atoms or representsphenyl and R⁴ represents hydrogen or alkyl having 1 to 4 carbon atoms orR³ and R⁴ together represent a —(CH₂)₅— chain and with a thiocyanate ofthe formula X—SCN  (IV),  in which X represents sodium, potassium orammonium, and reacting b) the resulting triazolidinethione derivative ofthe formula

 in which R¹, R², R³ and R⁴ are each as defined above with formic acid.2. The process according to claim 1, characterized in that the hydrazinederivative starting material used is2-(1-chloro-cyclopropyl)-1-(2-chloro-phenyl)-2-hydroxy-propyl-1-hydrazineof the formula


3. The process according to claim 1, characterized in that for carryingout the first step carbonyl compounds of the formula (III) are employedin which R³ represents methyl, ethyl, n-propyl, isopropyl, n-butyl,tert-butyl or phenyl and R⁴ represents hydrogen, methyl, ethyl, n-propylor n-butyl or R³ and R⁴ together represent a —(CH₂)₅— chain.
 4. Theprocess according to claim 1, characterized in that the reactioncomponent used for carrying out the first step is sodium thiocyanate orpotassium thiocyanate.
 5. Process according to claim 1, characterized inthat the first step is carried out at temperatures between 0° C. and120° C.
 6. The process according to claim 1, characterized in that thesecond step of the process according to the invention is carried out attemperatures between 80° C. and 150° C.